(1) Epithelial cells of the mammalian distal nephron are bathed by a hypertonic serosal milieu. Using the toad urinary bladder model, we studied how serosal hypertonicity affects cell volume regulation and the physiologic response to vasopressin. We have previously shown that vasopressin stimulation results in the transfer of water channels (membrane particle aggregates seen by freeze-fracture EM) from cytoplasmic to luminal membranes. Here we found that: a) serosal hypertonicity alone causes an increase in luminal membrane aggregates and water permeability; b) aggregate integrity is less well maintained without hormone; c) following an initial shrinkage, cell volume returns to normal in the continuous presence of hypertonicity; and d) serosal hypertonicity modifies the magnitude and time course of the water permeability responses to vasopressin. (2) Lymphocyte size and morphology vary widely in chronic lymphocytic leukemia. Lymphocyte nuclear areas from patients blood films were measured using a digitizing tablet and analyzed with a computer program. In part of this study, one patient's cells sampled 15 years apart, were compared. Histograms of nuclear size from the earlier film showed a bimodal distribution. Analysis of the later film showed a significant reduction in the proportion of the larger lymphocytes. (3) In cooperation with Hepatitis Lab, liver biopsies of experimentally infected chimps are prepared for EM and examined for evidence of changes induced by hepatitis viruses A and C. (4) Other studies: During the course of the year the EM laboratory responds to the requests of CBER staff members for short-term studies. These may involve examining cell cultures for the presence of contaminating organisms, determining @the presence (or absence) of viruses, verifying cell types in culture, preparing specimens, and exploratory pilot studies.